Role of mesenchymal stromal cell secretome on recovery from cellular senescence: an overview

Cellular senescence is intricately linked with numerous changes observed in the aging process, including the depletion of the stem cell pool and the decline in tissue and organ functions. Over the past three decades, efforts to halt and reverse aging have intensified, bringing rejuvenation closer to reality. Current strategies involve treatments using stem cells or their derivatives, such as the secretome. This article aims to highlight key points and evaluate the utilization of secretome derived from mesenchymal stromal cells (MSCs) as an antisenescent approach. Employing a quasi-systematic research approach, the authors conducted a comprehensive analysis based on a search algorithm targeting the in vitro effects of MSC-derived secretome on rescuing cells from a senescent state. Reviewing 39 articles out of 687 hits retrieved from PubMed and Scopus without a time limit, the authors synthesized information and identified common types of MSC-tissue sources utilized (including bone marrow-MSCs, umbilical cord-MSCs, iPSC-derived MSCs, adipose tissue-MSCs, dental pulp-MSCs, amniotic membrane-MSCs, placenta-MSCs, gingival-MSCs, urine-MSCs, and commercially available MSC lineages) from both human and other species (such as mice and rats). The authors also examined the forms of secretome tested (including conditioned media and extracellular vesicles), the cell types treated (MSCs or other cell types), methods/biomarkers of monitoring senescence/rejuvenation, and the mechanisms involved. Ultimately, this review underscores the proof-of-principle of the beneficial effects of MSC-derived secretome in reversing cellular senescence across various cell types. Such insights might aid the scientific community in designing improved in vitro and in vivo assays for future research and clinical validation of this promising cell-free therapy.